Preparation of 6-bromo-1,2-benzisothiazole_Kain Industrial Additive

Background and overview^[1]

6-Bromo-1,2-benzisothiazole can be used as a pharmaceutical synthesis intermediate. If 6-bromo-1,2-benzisothiazole is inhaled, move the patient to fresh air; if skin contact occurs, remove contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel unwell. ; If eye contact occurs, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

Preparation^[1]

1) A mixture of compound 280A (2g, 10mmol), hydroxylamine hydrochloride (830mg, 12mmol) and sodium acetate (656mg, 8mmol) in water (5mL) and ethanol (20mL) was stirred under nitrogen at 25°C. Keep it down for 5 hours. The solution was concentrated to dryness. The crude product was washed with water (5 mL) and dried to obtain compound 280B.

2) To a solution of compound 280B (717 mg, 3.3 mmol) in DMSO (10 mL) at 25°C, potassium carbonate (638 mg, 4.6 mmol) was added. The mixture was stirred at 120°C overnight. The solution was cooled to room temperature and extracted with ethyl acetate (100 mL × 2). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered and evaporated to give compound 6-bromo-1,2-benzisothiazole 280C.

Application

6-Bromo-1,2-benzisothiazole can be used as a pharmaceutical synthesis intermediate. If the following reaction occurs:

Compound 6-bromo-1,2-benzisothiazole 280C (197mg, 1mmol), compound 175B (334mg, 1.1mmol), potassium carbonate (414mg, 3mmol) and Pd(dppf)Cl2 (20mg, 0.04mmol) )mixture. Dioxane (10 mL) and water (2 mL) were stirred under nitrogen at 100 °C overnight. The solution was cooled to room temperature, adjusted to pH 4 with aqueous hydrochloric acid solution (6N, 2mL), and extracted with ethyl acetate (100mL×3). The organic layer was washed with water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered and evaporated to give compound 280D.

Main reference materials

[1](WO2015042397)GLUCOSYLCERAMIDESYNTHASEINHIBITORSFORTHETREATMENTOFDISEASES